The long-term objectives are to identify and study the different repair pathways used by cells to avoid spontaneous mitotic DNA damage, chromosome loss and mitotic recombination, using the yeast Saccharomyces cerevisiae as a model system for genetic and molecular studies. Chromosome loss and mitotic recombination lead to loss of heterozygosity (LOH), events that are associated with human disease and neoplastic growth of cells. Spontaneous DNA damage often leads to stalling of replication forks. Replication is resumed by repairing the blocking lesion, or bypass of the lesion. Bypass can involves recombination processes or post-replication repair (PRR). The components of these pathways and how they are integrated will be studied. There are three main areas of investigation that are proposed: 1) the contribution of recombination repair genes and DNA damage checkpoint functions to genomic stability, 2) the role of the PRR genes to genomic stability and overlap with the recombination repair functions, and 3) the role that sister chromatid cohesion plays in determining the type of repair pathway used to overcome replication fork stalling and spontaneous DNA damage repair.